circSMAD2 governs migration and epithelial-mesenchymal transition by inhibiting microRNA-9
circSMAD2 governs migration and epithelial-mesenchymal transition by inhibiting microRNA-9
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DOI：
10.1002/jcb.29638
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发表时间：
2019-12-30
影响因子：
4
通讯作者：
Yu, Lili
中科院分区：
文献类型：
--
作者：
Han, Ning;Ding, Lei;Yu, Lili
上皮-间充质转化（EMT）使癌症过程达到顶峰。研究发现，circular RNA-SMAD 2（circSMAD 2）通过调节microRNA（miR）来阻止EMT。在此，我们打算研究circSMAD 2-miR-9结在前列腺癌细胞中的作用。从20例前列腺癌患者中获得组织标本。用携带circSMAD 2或miR-9模拟物的质粒转染LNCaP和PC-3细胞。通过定量逆转录聚合酶链反应对circSMAD 2和miR-9进行定量。对细胞进行活力、增殖和迁移测定。通过研究SMAD 2的磷酸化、钙粘蛋白开关的改变和波形蛋白的积累来评估EMT过程。STAT和MEK/ERK途径，然后通过Western blot测定。我们发现肿瘤组织显示circSMAD 2减少。circSMAD 2的恢复抑制了LNCaP和PC-3细胞的增殖和迁移活性，并破坏了EMT过程。此外，circSMAD 2过表达的细胞显示miR-9减少。上调miR-9消除了circSMAD 2在增殖、迁移和EMT中的抑制作用。此外，circSMAD 2减弱了STAT 3、MEK和ERK的磷酸化，而miR-9模拟物恢复了磷酸化的表达。总之，miR-9抑制是circSMAD 2减弱前列腺癌细胞中的迁移和EMT过程所必需的。
Epithelial-mesenchymal transition (EMT) culminates the cancer process. Studies found circular RNA-SMAD2 (circSMAD2) impedes EMT by regulating microRNA (miR). Here, we intended to investigate the role of circSMAD2-miR-9 node in prostate cancer cells. Tissue specimens were procured from 20 patients with prostate cancer. LNCaP and PC-3 cells were transfected with the plasmid bearing circSMAD2 or miR-9 mimic. circSMAD2 and miR-9 were quantified by quantitative reverse transcription polymerase chain reaction. The cells were subjected to assays for viability, proliferation, and migration. EMT process was evaluated by investigating the phosphorylation of SMAD2, alteration of cadherin switch, and accumulation of vimentin. STAT and MEK/ERK pathways were then determined by Western blot. We found that the tumor tissues showed a decrement in circSMAD2. Restoration of circSMAD2 inhibited the proliferative and migratory activities, and impaired EMT process of LNCaP and PC-3 cells. Moreover, circSMAD2-overexpressed cells showed a decrease in miR-9. Upregulating miR-9 abolished the inhibitory role of circSMAD2 in proliferation, migration, and EMT. Furthermore, circSMAD2 abated the phosphorylation of STAT3, MEK, and ERK, while miR-9 mimic rehabilitated the phosphorylated expression. In conclusion, miR-9 inhibition is required for circSMAD2 to abate migration and EMT process in prostate cancer cells.